Effect Of Cytokines In Host Defense And Inflammation

1)在2011财年期间，该项目扩大到研究炎症细胞和液体在髓系抑制细胞活动中的可能作用，这些细胞被认为在肿瘤发生和免疫调节中发挥作用。在与Doug Kuhns(SAIC)的合作下，我们招募了7名正常受试者，成功地建立了我们的髓系抑制细胞功能的体外试验。在接下来的一年里，我们将确定各种原发免疫缺陷患者是否会表现出异常的髓系抑制活性。 2)在2011财年，我们在NIH协议#10-I-0123中登记了第一批患者，评估慢性肉芽肿性疾病中特定基因突变的受试者对干扰素-伽马的生化反应。这项研究将测试潜在突变和/或残留NADPH氧化酶活性不同的CGD患者亚群是否更有可能从干扰素-伽玛治疗中受益。干扰素-γ已在临床上用于CGD患者，以降低感染率。然而，这种昂贵药物作用的机制和CGD患者之间临床反应的广泛差异都不清楚。我们的假设是，只有特定的CGD患者亚组，特别是那些ROS水平较高的患者可能对干扰素治疗有效并受益于干扰素治疗。这项研究的完成可能会显著节省成本，并减少与干扰素治疗相关的发病率。

1) During FY2011, this project expanded to study the possible role of inflammatory cells and fluids in the activity of myeloid-derived suppressor cells thought to play a role in tumorigenesis and immunoregulation. In collaboration with Doug Kuhns (SAIC), we enrolled 7 normal subjects to successfully establish our in vitro assay of myeloid suppressor cell function. In the coming year, we will determine whether patients with various primary immunodeficiencies may display abnormal myeloid suppressor activity. 2) During FY11, we enrolled our first patients in NIH Protocol #10-I-0123 Assessment of the Biochemical Response to IFN-gamma in Subjects with Specific Gene Mutations in Chronic Granulomatous Disease. This study will test whether subpopulations of CGD patients, differing in underlying mutation and/or residual NADPH oxidase activity, are more likely to benefit from IFN-gamma treatment. Interferon-gamma has been used clinically in CGD patients to reduce the rates of infection. However, neither the mechanism of this costly drugs actions nor the wide variation in clinical response among CGD patients is known. Our hypothesis is that only certain subgroups of CGD patients, specifically those with higher detectable levels of ROS may be responsive to and benefit from Interferon treatment. Completion of this study may result in significant cost savings and a reduction in morbidity associated with interferon treatment.